This project will examine the hypothesis that NMDA receptor hypofunction within hippocampal regions model[unreadable] central features of the cognitive symptoms of schizophrenia. Neuropsychological studies in schizophrenic[unreadable] patients have identified a core deficit in episodic memory and studies on animals strongly suggest an[unreadable] essential role for NMDA receptors in the hippocampus is the storage and recall of associations that underlie[unreadable] our capacity for episodic memory. The proposed studies will combine our own recent development of a[unreadable] novel protocol for the assessment of specific features of episodic memory in animals and a novel technique[unreadable] for spatially and temporally selective NMDA receptor knockout developed in Robert Greene's laboratory. In[unreadable] collaborative studies we will explore the role of NMDA receptors in specific components of the hippocampal[unreadable] circuit. We expect to dissociate a critical role for NMDA receptors in area CA3 in the association of stimuli[unreadable] and their context from a critical role for NMDA receptors in area CA1 in memory for sequential events. We[unreadable] also expect to dissociate a critical role for CA3 and CA1 NMDA receptors in "all-or-none" episodic memory[unreadable] retrieval from a crucial role for NMDA receptors in the perirhinal and entorhinal cortex in recognition based[unreadable] on a sense of familiarity. Finally, we expect to identify a selective role for CA3 NMDA receptors in the linking[unreadable] of related memories supporting inferences from memory. These findings will provide insights about the[unreadable] functional circuitry of hippocampal NMDA receptors, of strong relevance to other center projects that employ[unreadable] functional imaging, molecular and cellular biology, and computational modeling.